SERMs are a class of drugs with mixed estrogen agonist/antagonist effects that have great potential at targeting changes seen in the postmenopausal period. Raloxifene is effective in preventing bone loss and may prevent fractures in postmenopausal osteoporosis. It induces changes in lipoprotein concentrations that should be cardioprotective. It has no stimulatory effect on the uterus and is well tolerated. Raloxifene is an attractive alternative to HRT in preventing postmenopausal bone loss, especially for women that are more concerned about the risk of breast cancer or vaginal bleeding. Unanswered questions include raloxifene's effect on fracture incidence, cardiac events, and dementia; long-term safety data are also needed. Its potential role in the primary prevention of breast cancer also needs large, long-term studies. Tamoxifen has been used traditionally as adjuvant therapy for breast cancer, but new data indicate that it is effective in the primary prevention of breast cancer in women at increased risk. Its effects on bone and lipoproteins are attractive complementary effects when used in the subset of women at increased risk for breast cancer. New generations of SERMs are being developed that may have more potent estrogen agonist effects on bone and cardiovascular disease, or more potent antiestrogen effects, especially at the breast. There will likely be a selection of SERMs available, and the choice of SERM for a woman will be tailored to her specific issues and risk profile.